Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts

Joshua T. Mendell, Colette M.J. Ap Rhys, Harry C. Dietz

Research output: Contribution to journalArticle

Abstract

The mechanism by which disruption of reading frame can influence pre-messenger RNA (pre-mRNA) processing is poorly understood. We assessed the role of factors essential for nonsense-mediated mRNA decay (NMD) in nonsense-mediated altered splicing (NAS) with the use of RNA interference (RNAi) in mammalian cells. Inhibition of rent1/hUpf1 expression abrogated both NMD and NAS of nonsense T cell receptor β transcripts. In contrast, inhibition of rent2/hUpf2 expression did not disrupt NAS despite achieving comparable stabilization of nonsense transcripts. We also demonstrate that NAS and NMD are genetically separable functions of rent1/hUpf1. Additionally, rent1/hUpf1 enters the nucleus where it may directly influence early events in mRNA biogenesis. This provides compelling evidence that NAS relies on a component of the nonsense surveillance machinery but is not an indirect consequence of NMD.

Original languageEnglish (US)
Pages (from-to)419-422
Number of pages4
JournalScience
Volume298
Issue number5592
DOIs
StatePublished - Oct 11 2002

ASJC Scopus subject areas

  • General

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